Medicine is powered by knowledge, but how do we know what is true and what is not? How do we deal with uncertainty in a setting where outcomes are not closely related to known variables? For example, although there are a few people who have survived jumping or falling from an airplane at high altitude (http://zidbits.com/2010/12/can-you-survive-a-freefall-without-a-parachute/), it is a rare event. Thus, a test to determine how to prevent death from such a disaster would only take a small number of participants to see if a particular method works. In contrast, when considering a medical condition where a large fraction of people might seemingly "recover" without treatment, such as tuberculosis (http://www.who.int/mediacentre/factsheets/who104/en/print.html), how does one determine if a treatment is effective? In this talk, I will examine how we gained knowledge about tuberculosis as an example of a disease where a combination of observational scientific findings and clinical trial data are linked to advance knowledge. I will also discuss other examples of clinical trials challenges and the solutions to these challenges.

Medicine is powered by knowledge, but how do we know what is true and what is not? How do we deal with uncertainty in a setting where outcomes are not closely related to known variables? For example, although there are a few people who have survived jumping or falling from an airplane at high altitude (http://zidbits.com/2010/12/can-you-survive-a-freefall-without-a-parachute/), it is a rare event. Thus, a test to determine how to prevent death from such a disaster would only take a small number of participants to see if a particular method works. In contrast, when considering a medical condition where a large fraction of people might seemingly "recover" without treatment, such as tuberculosis (http://www.who.int/mediacentre/factsheets/who104/en/print.html), how does one determine if a treatment is effective? In this talk, I will examine how we gained knowledge about tuberculosis as an example of a disease where a combination of observational scientific findings and clinical trial data are linked to advance knowledge. I will also discuss other examples of clinical trials challenges and the solutions to these challenges.

Sepsis is a difficult diagnosis to make, even in the hospital, where a plethora of tests are available to assist the clinician. However, the diagnosis remains a challenging one, due to the very nature of sepsis: a shadowy shape-shifter notorious for its ability to hide in plain sight, eluding early diagnosis and treatment. For now, even in-hospital, there is no test with perfect sensitivity or specificity for sepsis. This is especially true in the prehospital environment, where we must rely on tools we can bring into the field: physical exam, point of care tests (lactate/venous gas), assessment of end-tidal CO2, and ultrasound.

The aim of prehospital sepsis care is twofold: First, early diagnosis of cases ranging from early sepsis to septic shock. Point of care testing is essential. Lactate can assist in identifying occult sepsis and may also be used to prognosticate. Measurement of EtCO2 serves two purposes: first, in systems where point of care lactate is not available, there is evidence suggesting that EtCO2 is a reasonable surrogate for lactate. Secondly, for spontaneously breathing patients, EtCO2 provides an accurate respiratory rate, a vital sign that is notoriously poorly assessed. Respiratory rate plays a key role in both SIRS and SOFA/qSOFA criteria for sepsis, making an accurate count essential. Ultrasound should also play a pivotal role in prehospital sepsis management. Much has been made of the prehospital FAST exam; however, the ability of POCUS to gauge fluid responsiveness and cardiac function is far more useful. Assessment of the IVC may aid in determining the value of volume resuscitation by helping to identify patients who are responsive to volume and those who would be better served by early initiation of vasopressors. Similarly, assessment of cardiac function may prove extremely useful in selecting a pressor. POCUS may also assist in differentiating sepsis from other etiologies by identifying a source, such as pneumonia.

The second fundamental aim is treatment equivalent to that available in-hospital, with judicious administration of balanced IV fluids guided by POCUS and clinical assessment of fluid responsiveness, early pressors (including push-dose pressors during RSI), and early antibiotics, particularly where transport times are significant. When sepsis is diagnosed by EMS, a “sepsis alert” should be communicated to the receiving hospital, in order to facilitate ongoing early, aggressive care upon arrival of the retrieval team. Advanced prehospital diagnosis and treatment can produce dramatic reductions in mortality from sepsis.

Normally the endothelium plays a key role in maintaining homeostasis. Systemic and pulmonary endothelial dysfunction in the setting of critical illness results in multiple organ dysfunction. In this presentation, the following will be reviewed;

1) Evidence for the role of endothelial dysfunction in the pathogenesis of critical illness. Systemic endothelial dysfunction is implicated in the pathophysiology of sepsis and trauma, pulmonary endothelial dysfunction is involved in the development of ARDS. 2) Methods used to assess endothelial function in critical illness will be reviewed. 3) Mechanisms by which interventions may modify endothelial function will be discussed. The future potential role for treatments to modulate endothelial function in the management of the critically ill will be speculated.

In summary the aim of this review will be to highlight an important role for endothelial dysfunction in the critically ill.

Bill Knight gives a superb 20 minute talk with the North American perspective on Organ Donation, brain death and management of the brain dead donor prior to organ donation. Bill is an neuro intensivist, pre-hospital and emergency physician from Cincinnati so he has a great global perspective.

Greg Kelly focuses on transferable skills from adult practice applicable to the collapsed neonate, taking us first through a systematic approach to the common underlying causes and the physiology behind them. He outlines a comprehensive approach to the clapped out baby even when the underlying cause isn't immediately clear and reassures us that there are plenty of simple interventions we can undertake.

Allow me to introduce to you this extraordinarily talented doctor. John Hinds became involved in our motorcycle racing medical team as a medical student and progressed to inspirational teacher and natural leader. He had a burning passion for improving the care of the injured and on qualification it was evident he was destined for greatness within the world of critical care. In his role as Delta 7 for the Northern Ireland Ambulance Service and as a travelling doctor at motorcycle races in Ireland Doc John brought the highest standards of care and compassion to the most unfortunate at their hour of greatest need. I took this young man as my pupil teaching him the role of motorcycle doctor and quickly realised this exceptional doctor was truly special. In truth the pupil quickly became the master and I had the privilege of 15 years of working alongside him as his wingman.